Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries

Oesophageal cancers (adenocarcinomas [AC] and squamous cell carcinomas [SCC]) are characterized by high incidence/mortality in many countries. We aimed to delineate its global incidence and mortality, and studied whether socioeconomic development and its incidence rate were correlated. The age-standardized rates (ASRs) of incidence and mortality of this medical condition in 2012 for 184 nations from the GLOBOCAN database; national databases capturing incidence rates, and the WHO mortality database were examined. Their correlations with two indicators of socioeconomic development were evaluated. Joinpoint regression analysis was used to generate trends. The ratio between the ASR of AC and SCC was strongly correlated with HDI (r = 0.535 [men]; r = 0.661 [women]) and GDP (r = 0.594 [men]; r = 0.550 [women], both p < 0.001). Countries that reported the largest reduction in incidence in male included Poland (Average Annual Percent Change [AAPC] = −7.1, 95%C.I. = −12,−1.9) and Singapore (AAPC = −5.8, 95%C.I. = −9.5,−1.9), whereas for women the greatest decline was seen in Singapore (AAPC = −12.3, 95%C.I. = −17.3,−6.9) and China (AAPC = −5.6, 95%C.I. = −7.6,−3.4). The Philippines (AAPC = 4.3, 95%C.I. = 2,6.6) and Bulgaria (AAPC = 2.8, 95%C.I. = 0.5,5.1) had a significant mortality increase in men; whilst Columbia (AAPC = −6.1, 95%C.I. = −7.5,−4.6) and Slovenia (AAPC = −4.6, 95%C.I. = −7.9,−1.3) reported mortality decline in women. These findings inform individuals at increased risk for primary prevention

Impact of inter- and intra-individual variation, sample storage and sampling fraction on human stool microbial community profiles

Stools are commonly used as proxies for studying human gut microbial communities as sample collection is straightforward, cheap and non-invasive. In large-scale human population surveys, however, sample integrity becomes an issue as it is not logistically feasible for researchers to personally collect stools from every participant. Instead, participants are usually given guidelines on sample packaging and storage, and asked to deliver their stools to a centralised facility. Here, we tested a number of delivery conditions (temperature, duration and addition of preservative medium) and assessed their effects on stool microbial community composition using 16S rRNA gene amplicon sequencing. The largest source of variability in stool community composition was attributable to inter-individual differences regardless of delivery condition. Although the relative effect of delivery condition on community composition was small compared to inter-individual variability (1.6% vs. 60.5%, permutational multivariate analysis of variance [PERMANOVA]) and temporal variation within subjects over 10 weeks (5.2%), shifts in microbial taxa associated with delivery conditions were non-systematic and subject-specific. These findings indicated that it is not possible to model or accurately predict shifts in stool community composition associated with sampling logistics. Based on our findings, we recommend delivery of fresh, preservative-free stool samples to laboratories within 2 hr either at ambient or chilled temperatures to minimise perturbations to microbial community composition. In addition, subsamples from different fractions of the same stool displayed a small (3.3% vs. 72.6% inter-individual variation, PERMANOVA) but significant effect on community composition. Collection of larger sample volumes for homogenisation is recommended

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: An update 2018

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Search for heavy resonances decaying into a Z or W boson and a Higgs boson in final states with leptons and b-jets in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

This article presents a search for new resonances decaying into a Z or W boson and a 125 GeV Higgs boson h, and it targets the νν¯¯¯bb¯¯, ℓ+ℓ−bb¯¯, or ℓ±νbb¯¯ final states, where ℓ = e or μ, in proton-proton collisions at s√ = 13 TeV. The data used correspond to a total integrated luminosity of 139 fb−1 collected by the ATLAS detector during Run 2 of the LHC at CERN. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Zh or Wh candidates for evidence of a localised excess in the mass range from 220 GeV to 5 TeV. No significant excess is observed and 95% confidence-level upper limits between 1.3 pb and 0.3 fb are placed on the production cross section times branching fraction of neutral and charged spin-1 resonances and CP-odd scalar bosons. These limits are converted into constraints on the parameter space of the Heavy Vector Triplet model and the two-Higgs-doublet model

Search for boosted diphoton resonances in the 10 to 70 GeV mass range using 138 fb−1 of 13 TeV pp collisions with the ATLAS detector

A search for diphoton resonances in the mass range between 10 and 70 GeV with the ATLAS experiment at the Large Hadron Collider (LHC) is presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 138 fb−1 at a centre-of-mass energy of 13 TeV recorded from 2015 to 2018. Previous searches for diphoton resonances at the LHC have explored masses down to 65 GeV, finding no evidence of new particles. This search exploits the particular kinematics of events with pairs of closely spaced photons reconstructed in the detector, allowing examination of invariant masses down to 10 GeV. The presented strategy covers a region previously unexplored at hadron colliders because of the experimental challenges of recording low-energy photons and estimating the backgrounds. No significant excess is observed and the reported limits provide the strongest bound on promptly decaying axion-like particles coupling to gluons and photons for masses between 10 and 70 GeV

Search for flavour-changing neutral current interactions of the top quark and the Higgs boson in events with a pair of τ-leptons in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for flavour-changing neutral current (FCNC) tqH interactions involving a top quark, another up-type quark (q = u, c), and a Standard Model (SM) Higgs boson decaying into a τ-lepton pair (H → τ+τ−) is presented. The search is based on a dataset of pp collisions at s√ = 13 TeV that corresponds to an integrated luminosity of 139 fb−1 recorded with the ATLAS detector at the Large Hadron Collider. Two processes are considered: single top quark FCNC production in association with a Higgs boson (pp → tH), and top quark pair production in which one of top quarks decays into Wb and the other decays into qH through the FCNC interactions. The search selects events with two hadronically decaying τ-lepton candidates (τhad) or at least one τhad with an additional lepton (e, μ), as well as multiple jets. Event kinematics is used to separate signal from the background through a multivariate discriminant. A slight excess of data is observed with a significance of 2.3σ above the expected SM background, and 95% CL upper limits on the t → qH branching ratios are derived. The observed (expected) 95% CL upper limits set on the t → cH and t → uH branching ratios are 9.4×10−4(4.8+2.2−1.4×10−4) and 6.9×10−4(3.5+1.5−1.0×10−4), respectively. The corresponding combined observed (expected) upper limits on the dimension-6 operator Wilson coefficients in the effective tqH couplings are Ccϕ < 1.35 (0.97) and Cuϕ < 1.16 (0.82)

Measurement of the properties of Higgs boson production at s√ = 13 TeV in the H → γγ channel using 139 fb−1 of pp collision data with the ATLAS experiment

Measurements of Higgs boson production cross-sections are carried out in the diphoton decay channel using 139 fb−1 of pp collision data at s√ = 13 TeV collected by the ATLAS experiment at the LHC. The analysis is based on the definition of 101 distinct signal regions using machine-learning techniques. The inclusive Higgs boson signal strength in the diphoton channel is measured to be 1.04+0.10−0.09 . Cross-sections for gluon-gluon fusion, vector-boson fusion, associated production with a W or Z boson, and top associated production processes are reported. An upper limit of 10 times the Standard Model prediction is set for the associated production process of a Higgs boson with a single top quark, which has a unique sensitivity to the sign of the top quark Yukawa coupling. Higgs boson production is further characterized through measurements of Simplified Template Cross-Sections (STXS). In total, cross-sections of 28 STXS regions are measured. The measured STXS cross-sections are compatible with their Standard Model predictions, with a p-value of 93%. The measurements are also used to set constraints on Higgs boson coupling strengths, as well as on new interactions beyond the Standard Model in an effective field theory approach. No significant deviations from the Standard Model predictions are observed in these measurements, which provide significant sensitivity improvements compared to the previous ATLAS results